1. Field
The invention relates to devices for activating an electronic controller of an iontophoretic delivery device.
2. Description of Related Art
Iontophoresis is the migration of ions when an electrical current is passed through a solution containing ionized species, usually the ionic form of a drug or other therapeutic agent. One particularly advantageous application of iontophoresis is the non-invasive transdermal delivery of ionized drugs into a patient. This is done by applying low levels of current to a patch placed on the patient""s skin, which forces the ionized drugs contained in the patch through the patient""s skin.
Passive transdermal patches, such as those used to deliver nitroglycerin for angina pectoris, estradiol for hormone replacement, and nicotine to stop smoking, can only use a limited number of drugs because they work by diffusion. Iontophoresis advantageously expands the range of drugs available for transdermal delivery, including, for example, parenteral drugs (e.g., peptides). Further, because the amount of drug delivered is proportional to the amount of current applied, the drug delivery rate can be precisely controlled by controlling the current, unlike the passive transdermal patches. This allows for more rapid delivery (onset) and drug reduction (offset) in the patient.
When compared to drug delivery by needle injection, iontophoresis has less physical and emotional trauma, pain and possibility of infection. Transdermal drug delivery by iontophoresis also avoids the risks and inconvenience of intravenous delivery. In addition, when compared to oral ingestion of drugs, drug delivery by iontophoresis bypasses the GI tract, thus reducing side-effects such as drug loss, indigestion and stomach distress and eliminating the need for swallowing the drug. Iontophoresis also avoids drug loss due to hepatic first pass metabolism by the liver that occurs when drugs are ingested.
Further, transdermal drug delivery by iontophoresis permits continuous delivery of drugs with a short half life and easy termination of drug delivery. Because iontophoresis is more convenient, there is a greater likelihood of patient compliance in taking the drug. Thus, for all of the above reasons, iontophoresis offers an alternative and effective method of drug delivery, and is a especially useful method for children, the bedridden and the elderly.
An iontophoretic drug delivery device includes a current source, such as a battery and current controller, and a patch. The patch includes an active reservoir and a return reservoir. The active reservoir contains the ionized drug, usually in a conductive gel. The return reservoir contains a saline gel and collects ions emanating from the patient""s skin when the drug is being delivered into the patient""s skin.
The patch also has two electrodes, each arranged inside the active and return reservoirs to be in respective contact with the drug and saline. The anode, or positive, electrode and the cathode, or negative, electrode are respectively electrically connected to the anode and cathode of the current source by electrical conductors. Either the anode electrode or the cathode electrode is placed within the drug reservoir, depending on the charge of the ionized drug. This electrode is designated as the active electrode. The other electrode is placed within the return reservoir, and is designated as the return electrode.
The active electrode has the same charge as the ionized drug to be delivered and the return electrode has a charge opposite the drug to be delivered. For example, if the drug to be delivered to the patient has a positive ionic charge, then the anode will be the active electrode and the cathode will be the return electrode. Alternatively, if the drug to be delivered has a negative ionic charge, then the active electrode will be the cathode and the return electrode will be the anode.
When current from the current source is supplied to the active electrode, the drug ions migrate from the drug gel in the reservoir toward and through the skin of a patient. At the same time, ions flow from the patient""s skin into the saline solution of the return reservoir. Charge is transferred into the return electrode and back to the current source, completing the iontophoretic circuit.
For example, in an iontophoresis device employing a negatively-charged drug ion Dxe2x88x92, the drug reservoir houses the cathode and ionized drug Dxe2x88x92, and the return reservoir houses the saline solution and the anode. Upon application of current to the electrodes, negatively-charged drug ions are repelled from the cathode, because the drug ions and the cathode have the same negative polarity, and flow through the patient""s skin. At the same time, positively-charged ions flow back into the drug reservoir, being attracted to the cathode, and negatively-charged ions flow from the skin into the return reservoir, since they are attracted to the anode.
An electronic current controller between the battery and the electrodes regulates the current from the battery so that the patch receives the correct amount of current to deliver the proper dosage. This controller may control the current output to the patch so that drug delivery is accomplished at a constant or varying rate, or over a short, long or periodic time interval. These controllers generally require relatively complex electrical circuits, sometimes including microprocessors, to meet the above requirements.
Mechanical switches have been used in controllers to disconnect the battery from the controller circuitry to prevent battery drain during device storage. These controllers need to be switched on at the time they are placed on the body in order to begin operating. This, however, may lead to delayed drug delivery because the physician, nurse or patient may not remember to turn on the switch, or to erroneous drug delivery if the switch is inadvertently turned off before the completion of the drug delivery cycle. In addition, in the case of a defective switch or a switch having poor electrical contact, there may be uncertainty as to whether or not the device is actually delivering the therapeutic agent, or whether or not the device can complete without interruption an entire drug delivery cycle.
Electrically-activated switches have also been used to turn on iontophoretic drug delivery devices. See, for example, the switch 80 shown in FIG. 2 of U.S. Pat. No. 4,808,152 (Sibalis), which activates the iontophoretic device when electrical contact is made between the skin and the electrode. See also U.S. Pat. No. 5,314,502 (McNichols et al.), which shows an iontophoretic device including a two-electrode patch, electronic activation circuitry and power generating circuitry. The device remains completely turned off until the patch is applied to the skin. At that time, the circuit between the patch electrodes closes, closing the electronic activation circuitry and causing the power generating circuitry to be activated, thereby activating the iontophoretic device. Because the touching of the skin acts as the switch, a mechanical switch is not required. This type of switch is also said to prevent current drain from the battery during device storage.
However, a problem may still exist because the device may be activated when in contact with a conductive surface other than a patient""s skin. In this case, the circuit between the electrodes will close and the device will be activated, resulting in the unnecessary waste of the therapeutic drug and generating uncertainty in the ability of the device to deliver an entire drug dosage. Another problem of iontophoretic devices using mechanical switches or touch-sensitive switches is that these devices are turned on manually. Because of this, multiple iontophoretic devices using mechanical switches or touch-sensitive switches cannot easily be turned on simultaneously, nor can an iontophoretic device be turned on remotely.
In addition, these switches do not take into consideration other factors which are important in iontophoretic drug delivery systems. For example, it is well known that the electrical impedance of epidermal skin tissue (xe2x80x9cskin impedancexe2x80x9d) varies greatly, depending on factors such as where the patch is applied onto the body, the presence of calluses or dermal abrasions at that location, ambient air conditions such as temperature and humidity, the amount of skin hydration caused by perspiration, and the age of the individual. Skin impedance also varies as the current flows during iontophoretic drug delivery. For example, an extremely dry skin-patch interface is undesirable and problematic because it results in a unusually high impedance, requiring too high of a voltage to maintain the proper current level. Alternatively, when a voltage within the device""s normal voltage range is applied to a high impedance load, a current well below the proper current level will result. Any of the above operating conditions may cause skin irritation or may reduce drug transport.
Other problems that may arise in turning on iontophoretic devices by the above-described conventional methods involve the delivery of drugs or medicaments containing peptides. These problems are caused by the ionic charge of the peptide at the pH level of the skin, or by ionic, hydrophobic or biological interactions between the peptide and skin proteases. Skin proteases are enzymes that break the peptides into their constituent components and are carried, for example, by a person""s perspiration. Both factors may reduce the peptide""s mobility and thus impair its delivery.
Accordingly, there is a need for improved methods of activating iontophoretic devices so that the user of the iontophoretic device has greater control of the device, as well as increased flexibility and reliability.
It is an object of the present invention to provide methods for turning on an iontophoretic drug delivery device that overcome the above-described problems. Activation of the iontophoretic drug delivery system may be based on one or more of the above-described factors that cause variations in skin impedance. Activation of the iontophoretic device may also based on the skin""s pH or the amount of skin perspiration, or both, to overcome problems when delivering peptides. Activation may also be based on other factors external to the controller that may influence the operation of the controller, such as gravity or certain environmental conditions.
It is another object of the present invention to provide an iontophoretic drug delivery device that prevents unintended power-drain when conventional mechanical switches or touch-sensitive switches are used.
In is still another object of the present invention to provide an iontophoretic drug delivery device that can be turned on remotely or to allow multiple iontophoretic drug delivery devices to be turned on simultaneously.
In one aspect of the present invention, an iontophoretic drug delivery device is provided which includes (1) a controller normally in an off or low-power consumption state, and (2) a patch including (a) a pair of electrodes, (b) an active reservoir for holding an ionizable drug for transdermal delivery to a patient and (c) a return reservoir. The patch is removable and electrically connectable to the controller, and delivers the drug to the patient when the patch is on the patient""s skin and when the controller is switched from the off or low-power consumption state to an operational state. This switching may be caused by electrically connecting the patch to the controller and activating a connector therebetween. This switching may also be caused by electrically activating an activation signal circuit connected to the controller.